Aminophenylcarbamates

ABSTRACT

New aminophenylcarbamates of the formula WHEREIN R1 represents an alkyl residue containing not more than three carbon atoms and R2 an alkyl residue containing two to four carbon atoms, have very good properties in combating insects and members of the order Acarina, but they possess especially outstanding properties in destroying blood-sucking arthropodes. These carbamates may be used as active ingredients in pesticidal preparations.

United States Patent Nikles [451 July 11, 1972 [54]AMINOPHENYLCARBAMATES [72] Inventor: Erwin Nikles, Liestal, Switzerland[73] Assignee: Clba-Geigy AG, Basel, Switzerland [22] Filed: Oct. 20,1969 [21] Appl. No.: 867,862

[30] Foreign Application Priority Data Oct. 25, i968 Switzerland..l6003/68 Oct. 31, I968 Switzerland ..l62l2/68 [52] US. .Cl. ..260/479C, 260/463, 260/574, 424/300 [51] Int. Cl ..C07c 125/06 [58] Field ofSearch ..260/479 C [56] References Cited OTHER PUBLICATIONS Heiss et al.Chem. Abstracts, Vol. 59 (I963), Page 2120 C.

Metcalf et al., Agricult. and Food Chem., (1965), pp. 22l- 225.

Primary Examiner-James A. Patten Attorney-Harry Goldsmith, Joseph G.Kolodny and Mario A Monaco ABSTRACT New aminophenylcarbamates of theformula oH,-NH-o 0- wherein R represents an alkyl residue containing notmore than three carbon atoms and R an alkyl residue containing two tofour carbon atoms, have very good properties in combating insects andmembers of the order Acarina, but they possess especially outstandingproperties in destroying bloodsucking arthropodes. These carbamates maybe used as active ingredients in pesticidal preparations.

10 Claims, No Drawings AMINOPHENYLCARBAMATES The present inventionrelates to preparations for combating blood-sucking arthropodes whichcontain, as the active component, at least one compound ofgeneralformula as the free base or in the form of one of its salts, wherein Rrepresents an alkyl residue containing not more than three carbon atomsand R, an alkyl residue containing two to four carbon atoms, togetherwith a carrier. As suitable carriers there may be mentioned solvents,diluents, dispersing agents, wetting agents, emulsifiers, thickeners aswell as further known pesticides.

The present invention also provides carbamates of the above formula (I)and their salts, on which the agents are based.

The present invention also provides a process for preparing thecarbamates of the above formula (I), which comprises reacting a phenolof formula with methylisocyanate or methylcarbamic acid chloride or byreacting an aminophenylcarbonate or aminophenylchlorocarbonate offormula X-CO-O with methylamine, in which formulae R and R have themeanings given above or represent substituents which can be convertedinto these quoted substituents by post-alkylation, X represents ahalogen atom, preferably a chlorine atom.

The phenols required as intermediate products can be manufactured by amethod known per se. It is, for example, possible to alkylateo-aminophenol in the amino group by means of an alkyl sulphate ordialkyl sulphate, alkyl tosylate or alkyl halide, during which anacid-binding agent may be added. A further method consists in thereductive alkylation of o-nitrophenol or o-aminophenol with an aldehydeor ketone and catalytically activated hydrogen. lf R and R, are notidentical, the alkylation reactions have to be carried out in two stageswith different alkylating agents. Especially pure monoalkylaminophenolsare obtained by alkylation and subsequent hydrolysis from1,3-benz0xazol-2-one.

The sequence of the synthesis stages hitherto described, up to the finalproduct, can also be changed and suited to the specific properties ofthe carbamates. For example, it is possible first to manufactureo-nitrophenyl-carbonate or onitrophenyl-N-methylcarbamate and then toreduce and alkylate these. in the latter case the new carbamates aredirectly obtained, and in the former case a reaction with methylamine isstill required.

The active component can be present not only as the free base but alsoin the form of a salt. Inorganic and organic acids can be used for thesalt formation, for example, sulphuric acid, hydrochloric acid,hydrobromic acid, nitric acid, phosphoric acid, oxalic acid, citricacid, methanesulphonic acid, toluenesulphonic acid, maleic acid,monochloracetic, dichloracetic and trichloractic acid and many others.Acid salts, for example, the acid sulphate, are distinguished by goodstability.

Those active substances of formula (I) in which R, represents a methyl,ethyl orpropyl residue and R an ethyl, propyl, isopropyl, butyl or see.butyl residue are preferred.

The new carbamates of formula (I), according to the invention, show verygood biocidal properties in general combating of insects and pests ofthe order Acarina, in each case in all their stages of development. Thuscicadas are destroyed even by using small amounts of the activesubstance. Fruit flies are completely killed at concentrations of 2.5ppm after one hour. The carbamates, however, generally possessexceptional pro perties in destroying blood-sucking arthropodes.

This group of pests is not so much sub-divided through particularclasses or orders but is especially characterized and defined by itsbehavior as parasites of warm-blooded animals.

Their effect on humans and animals is, alongside pure molestation, thatof potential carriers of diseases (vectors), which cause infections oroccur as intermediate hosts of excitants of diseases.

As the most important representatives, flies (stinging flies, animalflies, tsetse flies and others), mosquitoes (yellow fever mosquito,malaria mosquito and others), lice, bugs, fleas, and also ticks andmites should be mentioned.

The last-mentioned representatives of the order Acarina assume theirgreatest importance as ectoparasites for mammals and birds. However, theother groups of pests which have been mentioned also represent aconstant and outstanding threat to all animal stocks, whether cattle,sheep, goats, pigs, horses, poultry or other useful animals.

The compounds of formula (I), by themselves or in preparations, showboth a contact poison effect and an ingested poison efiect in the pestswhich are to be combattcd. For example,2-(methyl-isopropylamino)-phenyl-N-methyl-carbamate,2(ethyl-isopropylamino)-phenyl-N-methylcarbamate,2(methyl-ethyLamino)-phenyl-N-methylcarbamate, 2-diethyl-amino-phenyl-N-methylcarbamate,2-(isopropyl-npropylamino)-phenyl-N-methylcarbamate and2-(methylsec.butylamino)-phenyl-N-methylcarbamate are highly activeagainst bugs such as Rhodnius prolixus or Cimex lectularius, mosquitoessuch as Aedes aegypti or Anopheles stephensi, parasitary mites such asDermanyssus gallinae and ticks such as Boophilus microplus, Amblyommavariegatum. As the bases or in the form of their salts, especially theacid sulphates, the new carbamates are suitable for use as activecomponents in bait mixtures for combating flies.

The new preparations can be employed in the most diverse manner in asolid, liquid or gaseous form, for example, in the form of sprays,dusting powders and emulsions and also in socalled fly plates orflypapers which are impregnated with a solution of at least one of theactive substances.

Possible materials for the manufacture of directly sprayable solutionsof the compounds of general formula (I) are, for example, mineral oilfractions of high to medium boiling range, for example, Diesel oil orkerosene, coal tar oil and oils of vegetable or animal origin, as wellas hydrocarbons, for example, alkylated naphthalenes ortetrahydronaphthalene, optionally using xylene mixtures, cyclohexanols,ketones and also chlorinated hydrocarbons, for example, trichloroethaneand tetrachlorethane, trichlorethylene or trichlorobenzenes andtetrachlorobenzenes. Organic solvents of which the boiling point isabove C are advantageously used.

Aqueous application forms are especially appropriately manufactured fromemulsion concentrates, pastes or wettable spraying powders by addingwater. Possible emulsifiers or dispersing agents are non-ionic products,for example, condensation products of aliphatic alcohols, amines orcarboxylic acids having a long-chain hydrocarbon residue of about 10 to20 carbon atoms with ethylene oxide, for example, the condensationproduct of octadecyl alcohol and 25 to 30 mols of ethylene oxide, orthat of technical oleylamine and 15 mols of ethylene oxide or that ofdodecylmercaptan and 12 mols of ethylene oxide. Amongst the anionicemulsifiers which can be employed there may be mentioned: the sodiumsalt of dodecyl alcohol sulphuric acid ester, the sodium salt ofdodecylbenzenesulphonic acid, the potassium or tn'ethanolamine salt ofoleic acid or of abietic acid or of mixtures of these acids, or thesodium salt of a petroleum-sulphonic acid. Possible cationic dispersingagents are quaternary ammonium compounds, for example, cetylpyridiniumbromide, or dihydroxyethylbenzyldodecylammonium chloride.

Talc, kaolin, bentonite, calcium carbonate, calcium phosphate, but alsocharcoal, cork powder, wood flour and other materials of vegetableorigin can be employed for the manufacture of dusting agents andscattering agents, for example for combating mites in poultry. Themanufacture of the preparations in a granular form is also to berecommended for special uses. The various forms of use can be providedin the usual manner with additions of substances which improve thedistribution, the adhesion, the rain resistance or the penetratingpower; amongst these there may be mentioned: fatty acids, resin, glue,casein or alginates.

The preparations according to the invention can be employed bythemselves or together with customary pesticides, especiallyinsecticides, acaricides, nematocides, bactericides and fungicides.

The concentration of the active ingredient employed can vary within widelimits depending on the nature of the use. It is generally 0.01 percentby weight of 20 percent by weight for more dilute preparations, whilstmore concentrated preparations contain 20 percent by weight to 98percent by weight of active ingredient. Preparations of maximumconcentration are, say, used in the so-called ULV technique (ultra-lowvolume) with minimum amounts of additives. The ULV technique is employedwith very finely atomizing spraying equipments, preferably with the aidof aircraft.

The action of the carbamates according to the invention can be furtherincreases by synergistic agents. Sesamine, sesamex, piperonyl-cyclonene,piperonyl-butoxy, piperonal-bis[2-(2- butoxyethoxy)ethyl]acetate,sulphoxides, propyl-isome, N-( 2-ethylhexyl)-5-norbomene-2,3-dicarboxamide, octachlorodipropyl-ether,2-nitrophenyl-propargyl-ether, 4- chloro-2-nitrophenyl-propargyl-etherand 2,4,5- trichlorophenylpropargyl-ether are, for example, suitable forthis purpose.

The following Examples illustrate the invention. The parts denote partsby weight:

Manufacturing Example A 2-( lsopropyl-methyl-amino )-phenol 150 Parts ofisopropyl bromide are added in portions at 60 C, in a nitrogenatmosphere, to a stirred mixture of 123 parts of 2-methylaminophenol,200 parts by volume of dimethylformamide, 130 parts of 2,6-lutidine and48 parts of potassium iodide. Thereafter the mixture is stirred for 24hours at 90 C, cooled and poured onto 3000 parts by volume of ice water.The product is extracted with three times 500 parts by volume oftoluene. The toluene solution is repeatedly washed with water, driedover anhydrous sodium sulphate, filtered and evaporated. Oily2-(isopropyl-methyl-amino)-phenol is obtained as the residue.

2-(lsopropyl-methyl-amino)phenyl-N-methylcarbamate (Compound No. l)

50 Parts of 2-(isopropyl-methyl-amino)phenol are dissolved in 300 partsby volume of carbon tetrachloride, mixed with 0.2 parts oftriethylenediamine and, at room temperature, with 19 parts ofmethylisocyanate added in portions, during which addition thetemperature rises. When the exothermic reaction has subsided, thesolution is kept for 14 hours at 40 C and is then evaporated, whereuponthe final product crystallises out. Melting point 65 to 70 C.

The following compounds analogously:

2. 2-(lsopropyl-ethyl-amino)phenyl-N-methylcarbamate,

oil.

can be manufactured 3.2-(lsopropyl-n-propyl-amino)phenyl-N-methylcarbamate, oil.

4. 2-(Sec.butyl-methyl-amino)phenyl-N-methylcarbamate,

oil. NMR-spectrum measured in CC]. (8-values):

m=0.61.2,6H en n Ami-5L3),

m= 1.2- 1.8, 2H -g,-ci-i,

m=3.03.5, 1 H egg-0H.)

b 6.0 6.5, 1 H (COlfi) m 7.7 8.2, 4 H (aromat. H).

5. 2-(Methyl-n-propyl-amino)-phenyl-N-methylcarbamate,

oil.

6. 2-(Methyl-n-butyl-amino)-phenyl-N-methylcarbamate,

oil.

7. 2-(Ethyl-methyl-amino)-phenyl-N-methylcarbamate,

melting point 66 to 68 C.

8. 2-Diethylaminophenyl-N-methylcarbamate, oil. NMR-spectrum measured inCC], (8-values): t= 1.02, 6 H (two CH CH (.I= 7 Hz), d= 2.89, 3 H(CONHCH (J 5 Hz), q= 3.12, 4 H (two CH -CH (.l 7 Hz), b= 5.05.3,1H(-CONH),

m 6.9 7.4, 4 H (aromat. H).

Manufacturing Example B Manufacture of the acidsulphate of the compoundNo. 4

10.2 Parts of 96 percent strength sulphuric acid are diluted with 44.9parts of water whilst cooling. 23.6 Parts of 2-(sec.butyl-methyl-amino)-phenyl-N-methylcarbamate are introduced whilststirring, whereupon a clear solution of the acid sulphate is immediatelyobtained.

Formulation Examples Dusting agents Equal parts of an active substanceaccording to the invention and of precipitated silica are finely ground.Dusting agents preferably containing one to six percent of activesubstance can be manufactured therefrom by mixing with kaolin or talc.Spraying powders In order to manufacture a spraying powder, thefollowing components are for example mixed and finely ground:

50 parts of active substance according to the present invention 20 partsof HlSlL (highly adsorbent silica) 25 parts of Bolus alba (kaolin) 3.5parts of a reaction product of p-tert. octylphenol and ethylene oxideand 1.5 parts of sodium 1-benzyl-2-stearyl-benzimidazole-6,3'-

disulphonate. Emulsion concentrate Easily soluble active substances canalso be formulated as an emulsion concentrate according to the followinginstruction:

20 parts of active substance 70 parts of xylene and 10 parts of amixture of a reaction product of an alkylphenol with ethylene oxide andcalcium dodecylbenzenesulphonate are mixed. On dilution with water tothe desired concentration a sprayable emulsion is produced.

EXAMPLE 1 a. Concentration experiment Female mosquitoes are placed forsix hours on a coating of the substance to be tested, in Petri dishes ofll cm diameter. This coating is produced by treating the bottom of thedish with 1 ml of a solution of the substance in acetone and subsequentdrying for one hour. Solutions of 1,000, 100, and 1 ppm are employed,corresponding to a concentration of 1, 0.1, 0.01 and 0.001 mg of activesubstance/dish lmg/dish E l g/9.4 m). The mosquitoes are cooled in iceand counted out 10 at a time into the dishes. 4 repeats are run perconcentration. The evaluation takes place after 45, 90 and 360 minutes.

b. Time experiment: Test of the minimum exposure time 1.9 ml of asolution of the active substance in acetone, containing 1000 ppm ofactive substance, are uniformly distributed over a filter paper of size10 X l9 cm. After drying, the paper is rolled and pushed into a testtube into which 10 female mosquitoes, briefly anaesthetised with CO areintroduced, the test tube thereafter being closed.

After an exposure time of 2, 4, 8, 16, 32, 60 or 120 minutes themosquitoes are again briefly anaesthetised and introduced into a cleanPetri dish with fodder (honey water).

An evaluation is made after 24 hours. The minimum exposure time is takento be the time at which 100 percent mortality can still be observed.

The following results are obtained from the two experiments:

Compound Total mortality (L IOO) Minimum Action against blood-suckingbugs (Rhodnius prolixus) The experimental arrangement corresponds tothat of Example l a). One hour after treatment of the Petri dish, 10bugs of the third larvae stage (LI-3) are exposed therein for 24 hours.The action of the active substance coating is ascertained after 45, 90,360 minutes, and 24 hours. Two repeats are run per concentration.

Compound Total mortality L,l00) No. at

after 1 0.01 mg/dish 360 mins.

4 0.01 mg/dish 45 mins.

5 0.0l mg/dish mins.

7 0.01 mg/dish 360 mins.

8 0.0l mg/dish 360 mins.

What we claim is:

1. Compounds of the formula C H;-NHC 0-0 wherein R represents an alkylresidue containing his: more than three carbon atoms and R an alkylresidue containing two to four carbon atoms.

2. Compounds of the formula accordlng to claim 1, wherein

2. Compounds of the formula according to claim 1, wherein R1 representsa methyl, ethyl, or propyl residue and R2 an ethyl, propyl, isopropyl,butyl or sec. butyl residue.
 3. The compound2-(isopropyl-ethyl-amino)-phenyl-N-methylcarbamate according to claim 1.4. The compound 2-(isopropyl-n-propyl-amino)-phenyl-N-methylcarbamateaccording to claim
 1. 5. The compound2-(sec.butyl-methyl-amino)-phenyl-N-methylcarbamate according toclaim
 1. 6. The compound2-(methyl-n-propyl-amino)-phenyl-N-methylcarbamate according to claim 1.7. The compound 2-(methyl-n-butyl-amino)-phenyl-N-methylcarbamateaccording to claim
 1. 8. The compound2-(ethyl-methyl-amino)-phenyl-N-methylcarbamate according to claim
 1. 9.The compound 2-diethylaminophenyl-N-methylcarbamate according toclaim
 1. 10. The compound2-(isopropyl-methyl-amino)-phenyl-N-methylcarbamate according to claim1.